InTERTwined: how promoter mutations impact BRAF-driven thyroid cancers.

Thyroid cancers are often initiated by the acquisition of a BRAF mutation. BRAF-driven thyroid tumors display a wide range of behaviors, from the slow-growing papillary carcinomas to the highly aggressive anaplastic. Mutations in the promoter of (telomerase reverse transcriptase) gene were discovered a decade ago and identified as prevalent events in thyroid cancers. Multiple studies showed that promoter mutations, particularly when co-occurring with BRAF, are markers of poor prognosis across thyroid cancer subtypes, and can be implemented for routine clinical stratification. Mechanistically, promoter mutations reactivate telomerase expression via the differential recruitment of transcriptional complexes. Re-expression of TERT impacts tumor biology, plausibly via both the well-known function of telomerase maintaining telomeres and by affecting other cancer-relevant processes.